Protective effect of FK866 on acute liver injury induced by acetaminophen and its mechanism

Abstract:

Objective：To investigate the protective effect of FK866 on acute liver injury（ALI） induced by acetaminophen（APAP） and its mechanism. Methods：Twenty-four male C57BL/6 mice（6-week-old） were randomly divided into the control group，FK866 group，APAP group and FK866+APAP group. The activities of alanine aminotransferase（ALT） and aspartate aminotransferase（AST） in serum were determined by colorimetric method，the pathological changes of liver by HE（hematoxylin eosin） staining，the levels of tu－mor necrosis factor-α（TNF-α），interleukin-6（IL-6） and interleukin-1β（IL-1β） by ELISA，and the expression of nicotinamide phosphoribosyltransferase（NAMPT） by Western blot. Results：In the FK866+APAP group，the serum activities of ALT and AST were （13.969±0.290） and （7.150±0.669） IU/L respectively and significantly lower than those of the APAP group（ALT：F=364.709，P=0.000；AST：F=130.398，P=0.000）. The lobular structure was clear，the cell degeneration was mild，and no obvious congestion was observed in FK866-treated group. Furthermore，the serum levels of IL-6，IL-1β and TNF-α were （176.333±0.775），（79.765±1.000） and （147.083±1.000） pg/mL respectively，indicating the inflammatory factors were notably inhibited by FK866（F=207.106，P=0.000；F=165.027，P=0.000；F=118.636，P=0.000）. The expression of NAMPT protein was also down-regulated. Conclusion：FK866 can protect against the acute liver injury induced by APAP，and the anti-inflammatory effects may be involved in it.